Pain transduction involves T-type calcium channels, namely the Cav3.2 subtype. Increased T-type channel expression or activity may contribute to visceral hypersensitivity in IBS, according to experimental research and clinical evidence, and their blockage may reduce discomfort. Thus, this study assessed the therapeutic potential of ethosuximide, a T-type calcium channel blocker, for abdominal discomfort associated with IBS.
Adults with abdominal discomfort severity evaluated at least 4 out of 10 over a 7-day run-in phase who met the Rome IV criteria for IBS and were receiving treatment in ten gastroenterology departments in French university hospitals were the participants. For 12 weeks, patients were randomly assigned to receive either ethosuximide or a placebo every day.
The main outcome measure was the responder rate, which was defined as a minimum 30% decrease in the average intensity of abdominal pain linked to a Subject Global Assessment of Relief score of at least 4 (i.e., significantly or totally alleviated). Safety, the intensity of IBS symptoms, and quality of life were secondary objectives.
124 of the 161 patients that were enrolled were randomly assigned to receive either ethosuximide or a placebo. The median (IQR) length of IBS was 5.0 (1.4-10.6) years, the mean (SD) severity of stomach pain was 6.0 (1.0), the mean (SD) age was 43.7 (14.9) years, and 72 (58.1%) were female. Responder rates did not differ significantly across groups in the intent-to-treat analysis (17 of 64 patients [26.6%] for ethosuximide vs. 14 of 60 patients [23.3%] for placebo; relative risk, 1.14; 95% CI, 0.61-2.11).
When compared to a placebo, ethosuximide was less well tolerated, with higher discontinuation rates (30 patients [46.9%] vs. 13 patients [21.7%]; P =.003) and more adverse events (261 of 463 adverse events reported overall [56.4%] were determined to be caused by ethosuximide; P <.001), most frequently headaches, nausea, and sleep disturbances. Overall, Ethosuximide did not significantly improve the treatment of IBS-related stomach discomfort, according to this randomized clinical research.
Reference:
Kerckhove, N., Zerbib, F., Chambaz, M., Mion, F., Zalar, A., Goutorbe, F., Coffin, B., Payen, L., Roman, S., Guilngar, A., Pereira, B., Dualé, C., Dapoigny, M., Melchior, C., Scanzi, J., & IBSET Investigator Group (IIG). (2026). Ethosuximide and irritable bowel syndrome-related abdominal pain: A randomized clinical trial: A randomized clinical trial. JAMA Network Open, 9(1), e2551368. https://doi.org/10.1001/jamanetworkopen.2025.51368
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